POS1410 PROTEOMIC ANALYSIS OF CUTANEOUS LUPUS ERYTHEMATOSUS AND DERMATOMYOSITIS DERMAL INFILTRATE REVEALS DIFFERENTIALLY EXPRESSED CANONICAL PATHWAYS
Authors: A. Häyry, T. Niewold, A. Meves, J. Lehman, K. Popovic-Silwerfeldt, C. Charlesworth, B. Madden, E. Svenungsson, V. Oke
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Cutaneous lupus erythematosus (CLE) and dermatomyositis (DM) are autoimmune diseases with characteristic cutaneous rashes. Both are histopathologically characterized by interface dermatitis and they are difficult and sometimes impossible to differentiate based on skin biopsies. The specific pathogenesis of both conditions remains enigmatic. <h3>Objectives</h3> To systematically identify patterns of protein expression in CLE and DM dermal infiltrate that differentiate the two conditions from each other. <h3>Methods</h3> Punch biopsies were obtained from lesional skin from 6 patients with CLE and 5 patients with DM. Healthy or unaffected skin from 6 individuals was used as control material. Laser capture microdissection was used to isolate 1,000,000μm2 of tissue within the LE and DM dermal inflammatory infiltrates or control dermis. The samples were analyzed by nano-LC tandem mass spectrometry. Qiagen Ingenuity pathway analysis was performed based on the obtained proteomic database, and identified canonical pathways were compared between CLE, DM, and controls. <h3>Results</h3> Comparing CLE vs controls we identified 246 pathways, while 51 of them were enriched (threshold p&lt;0.05). Comparing DM vs controls 200 pathways were identified, while 72 were enriched. Canonical pathways enriched in both CLE and DM were those involved in antigen presentation, protein ubiquitination, acute phase response, interferon signaling, GP6 signaling, tRNA charging, and B cell development. Analysis of CLE vs DM showed 237 pathways, 70 of which were enriched (p&lt;0.05). The top differentially enriched canonical pathways in CLE compared to DM included EIF2 signaling, complement system, LXR/RXR and FXR/RXR activation, acute phase response signaling, mTOR and granzyme A signaling, clathrin mediated endocytosis signaling, and coagulation system. <h3>Conclusion</h3> Canonical pathways enriched in both CLE and DM skin are associated with activation of innate and adaptive immune systems, including the interferon system. A major difference between CLE and DM was that the EIF2 pathway, involved in cellular stress and induction of cell death, was enriched in CLE. Enriched granzyme A signaling indicates cytotoxic T lymphocyte activity in CLE, which is in line with that the top differentially upregulated cytokine in CLE in the proteomics was IL-16 (1), as CD8 T lymphocytes are well-described expressors of IL-16. Further, results indicate differentially activated metabolic pathways and deposition of complement and coagulation components in CLE dermal infiltrate. <h3>Reference</h3> [1]Niewold TB, Meves A, Lehman JS, <i>et al.</i> Proteome study of cutaneous lupus erythematosus (CLE) and dermatomyositis skin lesions reveals IL-16 is differentially upregulated in CLE. <i>Arthritis Res Ther</i> 2021;23:132. doi:10.1186/s13075-021-02511-0 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Aliisa Häyry: None declared, Timothy Niewold: None declared, Alexander Meves: None declared, Julia Lehman: None declared, Karin Popovic-Silwerfeldt: None declared, Cristine Charlesworth: None declared, Benjamin Madden: None declared, Elisabet Svenungsson Shareholder of: AstraZeneca, Pfizer, Speakers bureau: Janssen, Grant/research support from: Grant support from Merck, Vilija Oke Speakers bureau: Novartis, Paid instructor for: Jansen, Astra Zeneca, UCB, Eli Lilly and Abbvie.